Xylose derivatives and preparation thereof

ABSTRACT

NOVEL AND NOVEL XYLOSE DERIVATIVES AND PREPARATION THEREOF, REPRESENTED BY THE GENERAL FORMULA   2-(R1-O-),3-HO,4-(R2-O-),5-(R3-O-CH2-)TETRAHYDROFURAN   WHEREIN R1 IS AN ALKYL OR ARALKYL RADICAL HAVING MORE THAN TWO CARBON ATOMS AND EACH OF R2 AND R3 IS AN ALKYL, ARALKYL OR ARACYL RADICAL. THE NEW XYLOSE DERIVATIVES ARE EFFECTIVE FOR MEDICAL TREATMENT OF INFLAMMATION OF EDEMA CAUSED BY ACETYLCHOLINE, HISTAMINE AND BRADYKININ.

United States Patent Office 3,586,664 XYLOSE DERIVATIVES AND PREPARATION THEREOF Shigeharu Kohno and Isao Yamatsu, Tokyo, Japan, as-

gignors to Eisai Kabushiki Kaisha, Bunkyo-ku, Tokyo,

apan N Drawing. Filed Mar. 19, 1969, Ser. No. 808,648 Int. Cl. C07c 47/18 US. Cl. 260-210R Claims ABSTRACT OF THE DISCLOSURE New and novel xylose derivatives and preparation thereof, represented by the general formula wherein R is an alkyl or aralkyl radical having more than two carbon atoms and each of R and R is an alkyl, aralkyl or aracyl radical. The new xylose derivatives are effective for medical treatment of inflammation and edema caused by acetylcholine, histamine and bradykinin.

This invention relates to a process for the synthetic preparation of new and novel xylose derivatives, i.e., xylofuranoside represented by the general formula R 0 CH2 0 (a) Antagonistic effects of Compound-A against contractions of the intestinal canal removed from guinea pig according to Magnus method:

Antagonistic efieet Concen- (percent) of tration Compound-A Substance applied (S/ml (30 S/ml.) (100 S/ml.)

Histamine 0. 1 90 100 Acetylcholine 0. 1 25 100 Bradykinin 0. 1 95 100 3,586,664 Patented June 22., 1971 (b) Repressive effect of Compound-A on dextran edema of guinea pig:

Effect observed Ing./kg., after Repressive i.p. adminiseflect Compound tration (percent) Control 0 0.5 1 l6 Compound-A g 3 2 0 5 1 18 Do l. 300 1 1 24 2 l 21 3 1 l7 1 At P=0.05, asignificant effect was observed as compared with control As is evident from the abovementioned tests, the new compounds obtained by the process of the present invention are effective as antiflammatory-antiedematous agent.

The new compounds of the present invention are prepared according to the following reaction.

EXAMPLE 1 Production of ethyl 3,5-dibenzyl-D-xylofuranoside 13 grams of 3,5-dibenzyl-1,2-isopropylidene xylofuranose were refluxed with stirring in ml. of 1% ethanolic hydrogen chloride solution for one and half an hour. The reaction mixture was neutralized with basic lead carbonate and filtered. Upon concentration of the filtrate, the residue was subjected to vacuum distillation and collected a fraction boiling at 205207 C./0.3 mm./Hg. There was thus obtained the compound aimed at.

AnaZysis.C I-I O Calculation (percent): C, 70.42; H, 7.26. Found (percent): C, 70.48; H, 7.19.

3,5-dibenzyl-1,2-isopropylidene xylofuranose employed as the starting material in the above example was prepared as follows:

21.5 grams of 1,2-isopropylidene-D-xylofuranose were dissolved in 250 ml. of benzyl chloride. To the solution were added 100 grams of pulverized potassium hydroxide and the whole was heated to 80 C. for hours. The reaction mixture was poured onto ice-water, extracted with a sufficient amount of chloroform. The extract was concentrated by distillation in order to remove the solvent. The residue was then distilled under reduced pressure and a fraction boiling at 200203 C./O.3 mm./Hg was collected.

EXAMPLE 2 Preparation of n-propyl-3,S-dibenzyl-D-xylofuranoside 13 grams of 3,5-dibenzyl-l,2-isopropylidene-D-xylofuranos'e were reacted with 120 ml. of 1% propanolic hydrogen chloride solution in accordance with the procedure disclosed in the preceding example. The fraction boiling at 205 -207 C./0.05 mm./Hg was thus obtained as the product aimed at.

Analysis.-C H O Calculation (percent): C, 71.00; H, 7.51. Found (percent): C, 70.48; H, 7.19.

EXAMPLE 3 Preparation of 1,3,5-tribenzyl-D-xylofuranoside EXAMPLE 4 Preparation of ethyl 3,5-dibenzoyl-D-xylofuranoside grams of 3,5-dibenz0yl-1,2-isopropylidene-D- xylofurar'iose were dissolved in 110 ml. of 1% ethanolic hydrogen chloride solution. The solution was further worked up in accordance with the procedure disclosed in Example 1.

Analysis of the product thus obtained was as follows:

C H O .Calculation (percent): C, 62.98; H, 6.07. Found (percent): C, 62.79; H, 5.96.

What we claim is:

1. A xylofuranoside represented by the general formula R30 CH2 0 H i HO 0 \CHC/ \OR wherein R is a lower alkyl radical containing at least two carbon atoms or benzyl radical and each of R and R groups is a lower alkyl, benzyl or benzoyl radical.

2. A xylofuranoside compound according to claim 1, namely, ethyl 3,S-dibenzyl-D-Xylofuranoside.

3. A xylofuranoside compound according to claim 1, namely, n-propyl-3,5-dibenzyl-D-xylofuranoside.

4. A xylofuranoside compound according to claim 1, namely, 1,3,5-tribenzyl-D-xylofuranoside.

5. A compound according to claim 1, namely, ethyl 3,5-dibenzoyl-D-xylofuranoside.

References Cited UNITED STATES PATENTS 2,235,786 3/1941 White 260210 3,073,788 1/ 1963 Hostettler et al. 260210 3,419,544 12/ 1968 Witzel et a1 260210 LEWIS GOTTS, Primary Examiner J. R. BROWN, Assistant Examiner US. Cl. X.R. 424- 

